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Localized microstimulation of primate pregenual cingulate cortex induces negative decision-making.

Amemori K, Graybiel AM - Nat. Neurosci. (2012)

Bottom Line: In healthy individuals, the pACC is involved in cost-benefit evaluation.We found that the macaque pACC has an opponent process-like organization of neurons representing motivationally positive and negative subjective value.This cortical zone could be critical for regulating negative emotional valence and anxiety in decision-making.

View Article: PubMed Central - PubMed

Affiliation: McGovern Institute for Brain Research, and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

ABSTRACT
The pregenual anterior cingulate cortex (pACC) has been implicated in human anxiety disorders and depression, but the circuit-level mechanisms underlying these disorders are unclear. In healthy individuals, the pACC is involved in cost-benefit evaluation. We developed a macaque version of an approach-avoidance decision task used to evaluate anxiety and depression in humans and, with multi-electrode recording and cortical microstimulation, we probed pACC function as monkeys performed this task. We found that the macaque pACC has an opponent process-like organization of neurons representing motivationally positive and negative subjective value. Spatial distribution of these two neuronal populations overlapped in the pACC, except in one subzone, where neurons with negative coding were more numerous. Notably, microstimulation in this subzone, but not elsewhere in the pACC, increased negative decision-making, and this negative biasing was blocked by anti-anxiety drug treatment. This cortical zone could be critical for regulating negative emotional valence and anxiety in decision-making.

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Distribution and dynamics of stimulations affecting decision-making. (a) Distribution of all stimulation sites in Ap-Av (left) and Ap-Ap (right) tasks (current amplitude: 70–80 µA). Sizes and colors of circles indicate percentage of stimulation-induced change in decision (red-orange hues, increased avoidance; blue hues, increased approach). Circle centers show locations of monopolar electrodes or mid-points between bipolar electrodes. Black dots represent sites with less than 3% stimulation-induced change. Data collected from both hemispheres of monkeys S and A. (b) Average changes in decision shown for all ventral bank effective sites (n = 13), expressed as t-scores. Black outline surrounds significant data (Fisher’s exact test, P < 0.01). Dotted lines indicate decision boundary (black: stimulation-off, white: stimulation-on). (c) Lack of stimulation-induced change in Ap-Ap task. (d) Lack of stimulation-induced difference in experiments with randomly presented stimulation-on trials (white dotted line) and stimulation-off trials (black dotted line). Yellow dotted line indicates decision boundary of collected data obtained in the stimulation-off trials in previous sessions. (e) Dynamics of stimulation effects on decisions for the 13 effective sites. Accumulated stimulation-on data were segregated into 5 temporal stages. Each bar represents the size of increase in avoidance in each of consecutive 50-trial stimulation-on blocks, relative to the 250-trial stimulation-off block.
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Figure 7: Distribution and dynamics of stimulations affecting decision-making. (a) Distribution of all stimulation sites in Ap-Av (left) and Ap-Ap (right) tasks (current amplitude: 70–80 µA). Sizes and colors of circles indicate percentage of stimulation-induced change in decision (red-orange hues, increased avoidance; blue hues, increased approach). Circle centers show locations of monopolar electrodes or mid-points between bipolar electrodes. Black dots represent sites with less than 3% stimulation-induced change. Data collected from both hemispheres of monkeys S and A. (b) Average changes in decision shown for all ventral bank effective sites (n = 13), expressed as t-scores. Black outline surrounds significant data (Fisher’s exact test, P < 0.01). Dotted lines indicate decision boundary (black: stimulation-off, white: stimulation-on). (c) Lack of stimulation-induced change in Ap-Ap task. (d) Lack of stimulation-induced difference in experiments with randomly presented stimulation-on trials (white dotted line) and stimulation-off trials (black dotted line). Yellow dotted line indicates decision boundary of collected data obtained in the stimulation-off trials in previous sessions. (e) Dynamics of stimulation effects on decisions for the 13 effective sites. Accumulated stimulation-on data were segregated into 5 temporal stages. Each bar represents the size of increase in avoidance in each of consecutive 50-trial stimulation-on blocks, relative to the 250-trial stimulation-off block.

Mentions: The effects of the microstimulation on the monkeys’ decision-making were remarkably selective. Stimulation was effective almost exclusively during performance of the Ap-Av task, it produced almost exclusively an increase in avoidance decisions, and it produced this effect almost exclusively for stimulation applied to the ventral bank of the cingulate sulcus (Figs. 6 and 7). Fig. 6 shows the results from a single stimulation site in the ventral bank region. Compared to the stimulation-off trials (Fig. 6a), the slope of the decision boundary during the stimulation-on trials was shifted rightward, and the number of avoidance decisions was increased (Fig. 6b). To quantify the effect of the stimulation, we introduced a spatial smoothing method and used Fisher’s exact probability test (Methods). We defined effective sites as those for which stimulation changed the monkey’s decisions significantly (P < 0.05) for at least 5% of all combinations of the two cues. Microstimulation in the ventral bank of the cingulate sulcus significantly increased avoidance choices for 16.6% of all cue combinations, most strongly for those indicating high airpuff strengths (Fig. 6c). Identically applied stimulation at the same site during Ap-Ap task performance did not induce any change in decision (Fig. 6d–f).


Localized microstimulation of primate pregenual cingulate cortex induces negative decision-making.

Amemori K, Graybiel AM - Nat. Neurosci. (2012)

Distribution and dynamics of stimulations affecting decision-making. (a) Distribution of all stimulation sites in Ap-Av (left) and Ap-Ap (right) tasks (current amplitude: 70–80 µA). Sizes and colors of circles indicate percentage of stimulation-induced change in decision (red-orange hues, increased avoidance; blue hues, increased approach). Circle centers show locations of monopolar electrodes or mid-points between bipolar electrodes. Black dots represent sites with less than 3% stimulation-induced change. Data collected from both hemispheres of monkeys S and A. (b) Average changes in decision shown for all ventral bank effective sites (n = 13), expressed as t-scores. Black outline surrounds significant data (Fisher’s exact test, P < 0.01). Dotted lines indicate decision boundary (black: stimulation-off, white: stimulation-on). (c) Lack of stimulation-induced change in Ap-Ap task. (d) Lack of stimulation-induced difference in experiments with randomly presented stimulation-on trials (white dotted line) and stimulation-off trials (black dotted line). Yellow dotted line indicates decision boundary of collected data obtained in the stimulation-off trials in previous sessions. (e) Dynamics of stimulation effects on decisions for the 13 effective sites. Accumulated stimulation-on data were segregated into 5 temporal stages. Each bar represents the size of increase in avoidance in each of consecutive 50-trial stimulation-on blocks, relative to the 250-trial stimulation-off block.
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Related In: Results  -  Collection

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Figure 7: Distribution and dynamics of stimulations affecting decision-making. (a) Distribution of all stimulation sites in Ap-Av (left) and Ap-Ap (right) tasks (current amplitude: 70–80 µA). Sizes and colors of circles indicate percentage of stimulation-induced change in decision (red-orange hues, increased avoidance; blue hues, increased approach). Circle centers show locations of monopolar electrodes or mid-points between bipolar electrodes. Black dots represent sites with less than 3% stimulation-induced change. Data collected from both hemispheres of monkeys S and A. (b) Average changes in decision shown for all ventral bank effective sites (n = 13), expressed as t-scores. Black outline surrounds significant data (Fisher’s exact test, P < 0.01). Dotted lines indicate decision boundary (black: stimulation-off, white: stimulation-on). (c) Lack of stimulation-induced change in Ap-Ap task. (d) Lack of stimulation-induced difference in experiments with randomly presented stimulation-on trials (white dotted line) and stimulation-off trials (black dotted line). Yellow dotted line indicates decision boundary of collected data obtained in the stimulation-off trials in previous sessions. (e) Dynamics of stimulation effects on decisions for the 13 effective sites. Accumulated stimulation-on data were segregated into 5 temporal stages. Each bar represents the size of increase in avoidance in each of consecutive 50-trial stimulation-on blocks, relative to the 250-trial stimulation-off block.
Mentions: The effects of the microstimulation on the monkeys’ decision-making were remarkably selective. Stimulation was effective almost exclusively during performance of the Ap-Av task, it produced almost exclusively an increase in avoidance decisions, and it produced this effect almost exclusively for stimulation applied to the ventral bank of the cingulate sulcus (Figs. 6 and 7). Fig. 6 shows the results from a single stimulation site in the ventral bank region. Compared to the stimulation-off trials (Fig. 6a), the slope of the decision boundary during the stimulation-on trials was shifted rightward, and the number of avoidance decisions was increased (Fig. 6b). To quantify the effect of the stimulation, we introduced a spatial smoothing method and used Fisher’s exact probability test (Methods). We defined effective sites as those for which stimulation changed the monkey’s decisions significantly (P < 0.05) for at least 5% of all combinations of the two cues. Microstimulation in the ventral bank of the cingulate sulcus significantly increased avoidance choices for 16.6% of all cue combinations, most strongly for those indicating high airpuff strengths (Fig. 6c). Identically applied stimulation at the same site during Ap-Ap task performance did not induce any change in decision (Fig. 6d–f).

Bottom Line: In healthy individuals, the pACC is involved in cost-benefit evaluation.We found that the macaque pACC has an opponent process-like organization of neurons representing motivationally positive and negative subjective value.This cortical zone could be critical for regulating negative emotional valence and anxiety in decision-making.

View Article: PubMed Central - PubMed

Affiliation: McGovern Institute for Brain Research, and Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

ABSTRACT
The pregenual anterior cingulate cortex (pACC) has been implicated in human anxiety disorders and depression, but the circuit-level mechanisms underlying these disorders are unclear. In healthy individuals, the pACC is involved in cost-benefit evaluation. We developed a macaque version of an approach-avoidance decision task used to evaluate anxiety and depression in humans and, with multi-electrode recording and cortical microstimulation, we probed pACC function as monkeys performed this task. We found that the macaque pACC has an opponent process-like organization of neurons representing motivationally positive and negative subjective value. Spatial distribution of these two neuronal populations overlapped in the pACC, except in one subzone, where neurons with negative coding were more numerous. Notably, microstimulation in this subzone, but not elsewhere in the pACC, increased negative decision-making, and this negative biasing was blocked by anti-anxiety drug treatment. This cortical zone could be critical for regulating negative emotional valence and anxiety in decision-making.

Show MeSH
Related in: MedlinePlus